Cancer is a broad group of diseases involving unregulated cell growth. In cancers, cells divide and grow uncontrollably, forming malignant tumors, which may invade nearby parts of the body. Cancer cells may also spread to distant parts of the body through the lymphatic system or bloodstream. There are over 200 different known cancers that affect humans.
Over-expression of epidermal growth factor receptor (EGFR) kinase is often associated with many cancers, including breast, lung, colorectal and head and neck cancers, and is believed to contribute to the malignant growth of these tumors. Activation of EGFR stimulated signaling pathways promote multiple processes that are potentially cancer-promoting, e.g., proliferation, angiogenesis, cell motility and invasion, decreased apoptosis and induction of drug resistance. Accordingly, intense efforts have been made to develop anti-tumor agents that target EGFR kinase, e.g., compounds that directly inhibit the kinase activity of the EGFR, as well as antibodies that reduce EGFR kinase activity by blocking EGFR activation. And some EGFR kinase inhibitors have been shown to improve tumor cell or neoplasia killing when used in combination with certain other anti-cancer or chemotherapeutic agents or treatment.
Although many anti-cancer agents are typically quite effective as initial therapy, it is common for patients to develop resistance with long-term exposure to these anti-cancer agents. Often, despite more aggressive second and third course of therapy using these agents, cancer of acquired resistance to anti-cancer agents displays increasing resistance and eventually becomes virtual invulnerable to these agents. Therefore, there is a continuing need to develop therapy for cancer with acquired resistance to anti-cancer agents.